Olfactory receptor 43 reduces hepatic lipid accumulation and adiposity in mice
- Authors
- Wu, Chunyan; Thach, Trung Thanh; Kim, Yeon-Ji; Lee, Sung-Joon
- Issue Date
- 4월-2019
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Olfr43; Olfactory receptor; (-)-carvone; Lipid accumulation; cAMP response element-binding protein
- Citation
- BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v.1864, no.4, pp.489 - 499
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
- Volume
- 1864
- Number
- 4
- Start Page
- 489
- End Page
- 499
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/66414
- DOI
- 10.1016/j.bbalip.2019.01.004
- ISSN
- 1388-1981
- Abstract
- Olfactory receptors are primarily expressed in nasal olfactory epithelium, but these receptors are also ectopically expressed in diverse tissues. In this study, we investigated the biological functions of Olfr43, a mouse homolog of human OR1A1, in cultured hepatocytes and mice to assess its functionality in lipid metabolism. Olfr43 was expressed in mouse hepatocytes, and Olfr43 activation by a known ligand, (-)-carvone, stimulated cAMP response element-binding protein (CREB) activity. In ligand-receptor binding studies using site-directed mutagenesis, ()-carvone binding required two residues, M257 and Y258, in Olfr43. In the mouse study, oral administration of ()-carvone for 5 weeks in high-fat diet-fed mice improved energy metabolism, including reductions in hepatic steatosis and adiposity, and improved glucose and insulin tolerance. In mouse livers and cultured mouse hepatocytes, Olfr43 activation simulated the CREB-hairy and enhancer of split 1 (HES1)-peroxisome proliferator-activated receptor (PPAR)-gamma signaling axis, leading to a reduction in hepatic triglyceride accumulation in the mouse liver. Thus, long-term administration of (-)-carvone reduces hepatic steatosis. The knockdown of Olfr43 gene expression in cultured hepatocytes negated these effects of (-)-carvone. In conclusion, an ectopic olfactory receptor, hepatic Olfr43, regulates energy metabolism via the CREB-HES1-PPAR gamma signaling axis.
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Collections - Graduate School > Department of Biotechnology > 1. Journal Articles
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